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Pulmonary drug delivery

Nazende Günday Türeli, Akif Emre Türeli, Marc Schneider
Design of Experiments (DoE) is a powerful tool for systematic evaluation of process parameters' effect on nanoparticle (NP) quality with minimum number of experiments. DoE was employed for optimization of ciprofloxacin loaded PLGA NPs for pulmonary delivery against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lungs. Since the biofilm produced by bacteria was shown to be a complicated 3D barrier with heterogeneous meshes ranging from 100nm to 500 nm, nanoformulations small enough to travel through those channels were assigned as target quality...
October 12, 2016: International Journal of Pharmaceutics
Moshe Bronshtein, Zeev Blumenfeld, Asaad Choury, Ayala Gover
OBJECTIVES: To assess the natural history and outcome of fetal pulmonary stenosis [PS] detected at 14 to 16 weeks gestation. METHODS: This is a retrospective study, in the years 2004-2015, with serial follow up during pregnancy. Patients referred for complete early fetal ultrasound including all fetal systems and a fetal echocardiogram. Ninety seven percent of the women were low risk, and 3% had risk factors such as maternal type 1 diabetes mellitus, exposure to teratogenic drugs or anomalies in previous pregnancies or in other family members...
October 14, 2016: Ultrasound in Obstetrics & Gynecology
Sylvia Natalie Kłodzińska, Petra Alexandra Priemel, Thomas Rades, Hanne Mørck Nielsen
Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa infections in CF patients are focused mainly on the delivery of antimicrobials to the lower respiratory tract, disregarding the sinuses. However, the sinuses constitute a reservoir for P. aeruginosa growth, leading to re-infection of the lungs, even after clearing an initial lung infection...
October 9, 2016: International Journal of Molecular Sciences
Thiago C Carvalho, John P McCook, Niven R Narain, Jason T McConville
Coenzyme Q10 (CoQ10) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. The aim of this study was to investigate the feasibility of preparing phospholipid-stabilized dispersions of the anticancer agent for continuous pulmonary delivery using a vibrating-mesh nebulizer. We determined the physicochemical properties (drug particle size distribution in dispersion, zeta potential, surface tension, and rheology) and compared the aerosolization profiles (nebulization performance, aerodynamic drug deposition and total emitted dose) of dispersions of CoQ10 prepared with different phospholipids...
October 9, 2016: International Journal of Pharmaceutics
E P Budgell, D Evans, K Schnippel, P Ive, L Long, S Rosen
BACKGROUND: Despite the large number of tuberculosis (TB) patients treated in South Africa (SA), there are few descriptions in the published literature of drug-susceptible TB patient characteristics, mode of diagnosis or treatment outcomes in routine public sector treatment programmes. OBJECTIVE: To enhance the evidence base for public sector TB treatment service delivery, we reported the characteristics of and outcomes for a retrospective cohort of adult TB patients at public sector clinics in the Johannesburg Metropolitan Municipality (JHB), SA...
September 5, 2016: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
Ronald Dahl, Alan Kaplan
BACKGROUND: In many countries worldwide, the long-acting anticholinergic drug tiotropium is available as a dry powder formulation delivered by means of the HandiHaler® inhalation device and as an aqueous solution delivered via the Respimat® Soft Mist™ Inhaler. Tiotropium HandiHaler® is a single-dose, dry powder, breath-actuated inhaler that provides delivered doses and lung deposition of tiotropium that are, over a wide range, not influenced by the severity of chronic obstructive pulmonary disease (COPD)...
October 11, 2016: BMC Pulmonary Medicine
Caina Xu, Huayu Tian, Ping Wang, Yanbing Wang, Xuesi Chen
A pH-sensitive co-delivery system was designed for the treatment of metastatic lung cancers by pulmonary delivery of doxorubicin (DOX) and Survivin siRNA. Conjugates PEI-BMPH-DOX (PMD) of polyethylenimine (PEI) with DOX were developed via a pH-sensitive hydrazine bond (3-maleimidopropionic acid hydrazide, BMPH). Furthermore, the PMD/Survivin siRNA complex nanoparticles were prepared by electrostatic interaction between cationic PMD and anionic Survivin siRNA. The drug release of DOX from PMD conjugates increased with decreasing pH values...
October 18, 2016: Biomaterials Science
Ching Kuo Tan, Gui Quan Say, James B Geake
Tiotropium bromide is a long-acting inhaled muscarinic antagonist used in patients with chronic respiratory disease. It has been available since 2002 as a single-dose dry powder formulation via the HandiHaler(®) dry powder inhaler (DPI) device, and since 2007 as the Respimat(®) SoftMist™ Inhaler (SMI). The latter is a novel method of medication delivery that utilizes a multidose aqueous solution to deliver the drug as a fine mist. Potential benefits include more efficient drug deposition throughout the respiratory tract, reduced systemic exposure, and greater ease of use and patient satisfaction compared with the use of HandiHaler DPI...
2016: Therapeutics and Clinical Risk Management
Nazareth Eliana Ceschan, Verónica Bucalá, María Verónica Ramírez-Rigo, Hugh David Charles Smyth
The inhalatory route has emerged as an interesting non-invasive alternative for drug delivery. This allows both pulmonary (local) or systemic treatments (via alveolar absorption). Further advantages in terms of stability, dose and patient preference have often lead researchers to focus on dry powder inhaler delivery systems. Atenolol is an antihypertensive drug with low oral bioavailability and gastrointestinal side effects. Because atenolol possesses adequate permeation across human epithelial membranes, it has been proposed as a good candidate for inhalatory administration...
September 30, 2016: European Journal of Pharmaceutics and Biopharmaceutics
Shao-Hui Lin, Wei Cui, Gui-Ling Wang, Shuai Meng, Ying-Chun Liu, Hong-Wei Jin, Liang-Ren Zhang, Ying Xie
Albumin-based nanoparticles (NPs) are a promising technology for developing drug-carrier systems, with improved deposition and retention profiles in lungs. Improved understanding of these drug-carrier interactions could lead to better drug-delivery systems. The present study combines computational and experimental methods to gain insights into the mechanism of binding of albuterol sulfate (AS) to bovine serum albumin (BSA) on the molecular level. Molecular dynamics simulation and surface plasmon resonance spectroscopy were used to determine that there are two binding sites on BSA for AS: the first of which is a high-affinity site corresponding to AS1 and the second of which appears to represent the integrated functions of several low-affinity sites corresponding to AS2, AS3, and AS8...
2016: Drug Design, Development and Therapy
Marius Hittinger, Nico Alexander Mell, Hanno Huwer, Brigitta Loretz, Nicole Schneider-Daum, Claus-Michael Lehr
Acute respiratory distress syndrome is linked to inflammatory processes in the human lung. The aim of this study was to mimic in vitro the treatment of lung inflammation by using a cell-based human autologous co-culture model. As a potential trial medication, we developed a pulmonary dry powder formulation loaded with interleukin-10 (IL-10), a potent anti-inflammatory cytokine. The inflammatory immune response was stimulated by lipopolysaccharide. The co-culture was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures )PADDOCC), to deposit the IL-10-loaded microparticles on the inflamed co-culture model at the air-liquid interface...
September 2016: Alternatives to Laboratory Animals: ATLA
Marius Hittinger, Julia Janke, Hanno Huwer, Regina Scherließ, Nicole Schneider-Daum, Claus-Michael Lehr
The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro. The choice of cell types, culture conditions and the experimental set-up, can affect the outcome and the relevance of a study...
September 2016: Alternatives to Laboratory Animals: ATLA
Di Wu, Chenhui Wang, Jiebing Yang, Hao Wang, Haobo Han, Aijun Zhang, Yan Yang, Quanshun Li
Porous PLGA microparticle for the coencapsulation of doxorubicin and miR-519c was successfully constructed through the water-oil-water emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. It has been characterized with high porous surface, adaptive aerodynamic diameter (<10 μm), favorable drug loading, and sustained release profile. The release supernatant exhibited a higher inhibition of cell proliferation than those from porous PLGA microparticles harboring a single component (doxorubicin or miR-519c), attributing to the enhanced induction of cell apoptosis and cell cycle arrest at S phase...
October 6, 2016: Molecular Pharmaceutics
Dianbo Li, Liping Gong
The aim of this study was to develop and characterize pirfenidone (PF)-loaded chitosan microspheres for lung targeting. The microspheres were prepared using the emulsion-solvent evaporation method and characterized by assessing morphology, particle size, and zeta potential. The microspheres had a spherical nature with highly smooth and integrated surfaces. The particle size of microspheres was 4.6±0.3 µm, and the zeta potential was 20.3±1.4 mV. The in vitro release results indicated that the obtained formulation of PF could reach the state of sustained release with a biphasic drug release pattern...
2016: Drug Design, Development and Therapy
Loreana Gallo, Verónica Bucalá, María Verónica Ramírez-Rigo
Sodium cromoglycate (SC) is an antiasthmatic and antiallergenic drug commonly used for chronic inhalation therapy; however, many daily intakes are required due to the fast drug clearance from airways. For these reasons, SC polymeric particles for inhalatory administration with adequate aerosolization and mucoadhesive properties were designed to prolong the drug residence time in the site of action. Sodium carboxymethylcellulose (CMCNa), sodium hyaluronate, and sodium alginate were selected to co-process SC by spray drying...
September 22, 2016: AAPS PharmSciTech
Kimberly J Dunham-Snary, Danchen Wu, Edward A Sykes, Amar Thakrar, Leah Rg Parlow, Jeffrey D Mewburn, Joel L Parlow, Stephen L Archer
Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation-perfusion matching and systemic oxygen delivery. In response to alveolar hypoxia, a mitochondrial sensor dynamically changes reactive oxygen species and redox couples in PASMC. This inhibits potassium channels, depolarizes PASMC, activates voltage-gated calcium channels, and increases cytosolic calcium, causing vasoconstriction...
September 16, 2016: Chest
Amy Z Stetten, Grace Moraca, Timothy E Corcoran, Stephanie Tristram-Nagle, Stephen Garoff, Todd M Przybycien, Robert D Tilton
It has long been known that deposited drops of surfactant solution induce Marangoni flows at air-liquid interfaces. These surfactant drops create a surface tension gradient, which causes an outward flow at the fluid interface. We show that aqueous phospholipid dispersions may be used for this same purpose. In aqueous dispersions, phospholipids aggregate into vesicles that are not surface-active; therefore, drops of these dispersions do not initiate Marangoni flow. However, aerosolization of these dispersions disrupts the vesicles, allowing access to the surface-active monomers within...
December 15, 2016: Journal of Colloid and Interface Science
Arzu Ari
There are several different types of drug delivery interfaces available on the market. Using the right interface for aerosol drug delivery to children is essential for effective inhalation therapy. However, clinicians usually focus on selecting the right drug-device combination and often overlook the importance of interface selection that lead to suboptimal drug delivery and therapeutic response in neonates and pediatrics. Therefore, it is necessary to critically assess each interface and understand its advantage and disadvantages in aerosol drug delivery to this patient population...
August 8, 2016: World Journal of Clinical Pediatrics
Stefan Wanning, Richard Süverkrüp, Alf Lamprecht
Spray-freeze-dried powders were suggested for nasal, epidermal (needle-free injection) or pulmonary application of proteins, peptides or nucleic acids. In spray-freeze-drying processes an aqueous solution is atomized into a refrigerant medium and subsequently dried by sublimation. Droplet-stream generators produce a fast stream of monodisperse droplets, where droplets are subject to collisions and therefore the initial monodispersity is lost and droplets increase in diameter, which reduces their suitability for pulmonary application...
September 1, 2016: European Journal of Pharmaceutical Sciences
Javier Ripollés, Angel Espinosa, Eugenio Martínez-Hurtado, Alfredo Abad-Gurumeta, Rubén Casans-Francés, Cristina Fernández-Pérez, Francisco López-Timoneda, José María Calvo-Vecino
BACKGROUND: The goal directed hemodynamic therapy is an approach focused on the use of cardiac output and related parameters as end-points for fluids and drugs to optimize tissue perfusion and oxygen delivery. Primary aim: To determine the effects of intraoperative goal directed hemodynamic therapy on postoperative complications rates. METHODS: A meta-analysis was carried out of the effects of goal directed hemodynamic therapy in adult noncardiac surgery on postoperative complications and mortality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology...
September 2016: Brazilian Journal of Anesthesiology
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